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Biomedical subjects

F Y Wu

Publications and source records attributed to F Y Wu.

At least 19 recordsLinked to original sources
PubMed2003

Duality relation for frustrated spin models.

We consider discrete spin models on arbitrary planar graphs and lattices with frustrated interactions. We first analyze the Ising model with frustrated plaquettes. We use an algebraic approach to derive the result that an Ising model with some of its plaquettes frustrated has a dual model which is an Ising model with an external field ipi/2 applied to the dual sites centered at frustrated plaquettes. In the case where all plaquettes are frustrated, this leads to the known result that the dual model has a uniform field ipi/2, whose partition function can be evaluated in the thermodynamic limit for regular lattices. The analysis is extended to a Potts spin glass with analogous results obtained.

Journal Article↗
PubMed2003

Chromium (VI) induced oxidative damage to DNA: increase of urinary 8-hydroxydeoxyguanosine concentrations (8-OHdG) among electroplating workers.

AIMS: To investigate the concentration of urinary 8-hydroxydeoxyguanosine (8-OHdG) among electroplating workers in Taiwan. METHODS: Fifty workers were selected from five chromium (Cr) electroplating plants in central Taiwan. The 20 control subjects were office workers with no previous exposure to Cr. Urinary 8-OHdG concentrations were determined using high performance liquid chromatography with electrochemical detection. RESULTS: Urinary 8-OHdG concentrations among Cr workers (1149.5 pmol/kg/day) were higher than those in the control group (730.2 pmol/kg/day). There was a positive correlation between urinary 8-OHdG concentrations and urinary Cr concentration (r = 0.447, p < 0.01), and urinary 8-OHdG correlated positively with airborne Cr concentration (r = 0.285). Using multiple regression analysis, the factors that affected urinary 8-OHdG concentrations were alcohol, the common cold, and high urinary Cr concentration. There was a high correlation of urinary 8-OHdG with both smoking and drinking, but multiple regression analysis showed that smoking was not a significant factor. Age and gender were also non-significant factors. CONCLUSION: 8-OHdG, which is an indicator of oxidative DNA damage, was a sensitive biomarker for Cr exposure.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Effect of genotoxic exposure to chromium among electroplating workers in Taiwan.

The objective of this study was to investigate the association between chromium (Cr) concentrations and sister chromatid exchanges (SCE) formation in Cr workers and to assess the effects of susceptible genes (glutathione S-transferase M1 and T1) on the frequency of deletion and SCE/cell. Urinary Cr concentration was significantly elevated in Cr workers (3.67 +/- 3.89 microg/g creatinine) compared to control group (1.21 +/- 1.16 microg/g creatinine, P < 0.01). There was also a significant difference of superoxide dismutase (SOD) levels between Cr workers (6.86 +/- 0.80 U/mg Hb) and controls (7.16 +/- 0.53 U/mg Hb, P < 0.01). The frequencies of SCE and high frequency cells (HFC) were significantly correlated with smoking habits and with duration of exposure to Cr. A significantly higher percentage (50%) of Cr workers had both the null GSTM1 and GSTT1 genotype as compared to 10% of the controls (P < 0.01). However, the chromosomal DNA damage effect of GSTM1 and GSTT1 genotypes, individually or in combination, was not revealed in Cr exposed workers.

Adolescent↗
PubMed2001

Ising model on nonorientable surfaces: exact solution for the Möbius strip and the Klein bottle.

Closed-form expressions are obtained for the partition function of the Ising model on an MxN simple-quartic lattice embedded on a Möbius strip and a Klein bottle. The solutions all lead to the same bulk free energy, but for finite M and N the expressions are different depending on whether the strip width M is odd or even. Finite-size corrections at criticality are analyzed and compared with those under cylindrical and toroidal boundary conditions. Our results are consistent with the conformal field prediction of a central charge c=1/2, provided that the twisted Möbius boundary condition is regarded as a free or fixed boundary.

Journal Article↗
PubMed2001

Spindle cell conversion by Kaposi's sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures.

Angiogenic Kaposi's sarcoma (KS) skin lesions found in both AIDS and non-AIDS patients are universally associated with infection by the presumed causative agent, known as KS-associated herpesvirus (KSHV) or human herpesvirus 8. KSHV genomes expressing latent state virus-encoded mRNAs and the LANA1 (latent nuclear antigen 1) protein are consistently present in spindle-like tumor cells that are thought to be of endothelial cell origin. Although the KSHV lytic cycle can be induced in rare latently infected primary effusion lymphoma (PEL) cell lines, the ability to transmit or assay infectious KSHV has so far eluded investigators. Here, we demonstrate that infection with supernatant virions derived from three different tetradecanoyl phorbol acetate-induced PEL cell lines can induce cultured primary human dermal microvascular endothelial cells (DMVEC) to form colonies of proliferating latently infected spindle-shaped cells, all of which express the KSHV-encoded LANA1 protein. Although their initial infectivity varied widely (JSC1 > > BC3 > BCP1), virions from all three cell lines produced distinctive spindle cell colonies and plaques without affecting the contact-inhibited cobblestone-like phenotype of adjacent uninfected DMVEC. Each infected culture could also be expanded into a completely spindloid persistently infected culture displaying aggregated swirls of spindle cells resembling those in KS lesions. Formation of new colonies and plaques was inhibited in the presence of phosphonoacetic acid or gangciclovir, but these antiherpesvirus agents had little effect on the propagation of already latently infected spindloid cultures. In persistently infected secondary cultures, patches of up to 10% of the spindloid cells constitutively expressed several early viral lytic cycle proteins, and 1 to 2% of the cells also formed typical herpesvirus DNA replication compartments, displayed cytopathic rounding effects, and expressed late viral antigens. We conclude that de novo KSHV infection induces a spindle cell conversion phenotype in primary DMVEC cultures that is directly associated with latent state expression of the LANA1 protein. However, these cultures also spontaneously reactivate to produce an unusual combination of both latent and productive but slow lytic cycle infection. The formation of spindle cell colonies and plaques in DMVEC cultures provides for the first time a quantitative assay for directly measuring the infectivity of KSHV virion preparations.

Antigens, Viral↗
PubMed2001

Interaction with the Epstein-Barr virus helicase targets Zta to DNA replication compartments.

Zta has a dual role in the Epstein-Barr virus (EBV) lytic cycle, acting as a key regulator of EBV lytic gene expression and also being essential for lytic viral DNA replication. Zta's replication function is mediated in part through interactions with the core viral replication proteins. We now show interaction between Zta and the helicase (BBLF4) and map the binding region to within amino acids (aa) 22 to 86 of the Zta activation domain. In immunofluorescence assays, green fluorescent protein (GFP)-tagged BBLF4 localized to the cytoplasm of transfected cells. Cotransfection of Zta resulted in translocation of BBLF4-GFP into the nucleus indicating interaction between these two proteins. However, Zta with a deletion of aa 24 to 86 was unable to mediate nuclear translocation of BBLF4-GFP. Results obtained with Zta variants carrying deletions across the aa 24 to 86 region indicated more than one contact site for BBLF4 within this domain, and this was reinforced by the behavior of the four-point mutant Zta (m22/26,74/75), which was severely impaired for BBLF4 interaction. Binding of BBLF4 to Zta was confirmed using GST affinity assays. In both cotransfection-replication assays and replication assays performed in EBV-positive P3HR1 cells, the Zta (m22/26,74/75) mutant was replication defective. In Zta-transfected D98-HR1 cells, replication compartments could be detected by immunofluorescence staining using anti-BMRF1 monoclonal antibody. Cells transfected with Zta variants that were defective for helicase binding still formed replication compartments, but Zta was excluded from these compartments. These experiments reveal a role for the Zta-helicase interaction in targeting Zta to sites of viral DNA replication.

DNA Helicases↗
PubMed2001

Origin-independent assembly of Kaposi's sarcoma-associated herpesvirus DNA replication compartments in transient cotransfection assays and association with the ORF-K8 protein and cellular PML.

Six predicted Kaposi's sarcoma virus herpesvirus (KSHV) proteins have homology with other well-characterized herpesvirus core DNA replication proteins and are expected to be essential for viral DNA synthesis. Intact Flag-tagged protein products from all six were produced from genomic expression vectors, although the ORF40/41 transcript encoding a primase-helicase component proved to be spliced with a 127-bp intron. The intracellular localization of these six KSHV replication proteins and the mechanism of their nuclear translocation were investigated. SSB (single-stranded DNA binding protein, ORF6) and PPF (polymerase processivity factor, ORF59) were found to be intrinsic nuclear proteins, whereas POL (polymerase, ORF9), which localized in the cytoplasm on its own, was translocated to the nucleus when cotransfected with PPF. PAF (primase-associated factor, ORF40/41), a component of the primase-helicase tripartite subcomplex together with PRI (primase, ORF56) and HEL (helicase, ORF44), required the presence of all five other replication proteins for efficient nuclear translocation. Surprisingly, even in the absence of a lytic cycle replication origin (ori-Lyt) and any known initiator or origin binding protein, the protein products of all six KSHV core replication genes cooperated in a transient cotransfection assay to form large globular shaped pseudo-replication compartments (pseudo-RC), which excluded cellular DNA. These pseudo-RC structures were confirmed to include POL, SSB, PRI, and PAF but did not contain any newly synthesized DNA. Similar to the human cytomegalovirus system, the peripheries of these KSHV pre-RC were also found to be surrounded by punctate PML oncogenic domains (PODs). Furthermore, by transient cotransfection, the six KSHV core replication machinery proteins successfully replicated a plasmid containing EBV ori-Lyt in the presence of the Epstein-Barr virus-encoded DNA binding initiator protein, ZTA. The KSHV-encoded K8 (ORF-K8) protein, which is a distant evolutionary homologue to ZTA, was incorporated into pseudo-RC structures formed by transient cotransfection with the six core KSHV replication genes. However, unlike ZTA, K8 displayed a punctate nuclear pattern both in transfected cells and at early stages of lytic infection and colocalized with the cellular PML proteins in PODs. Finally, K8 was also found to accumulate in functional viral RC, detected by incorporation of pulse-labeled bromodeoxyuridine into newly synthesized DNA in both tetradecanoyl phorbol acetate-induced JSC-1 primary effusion lymphoblasts and in KSHV lytically infected endothelial cells.

Amino Acid Sequence↗
PubMed2001

[Studies on the spectroscopic property of p-hydroxyphenol derivatives].

In the paper, properties of p-hydroxyphenol derivatives are described. The results prove that p-hydroxyphenol derivatives with different function groups show different spectroscopic properties. Some methods will be proposed to analyze a series of p-hydroxyphenol derivatives in blood or urine so as to identify the cancer mark.

Biomarkers, Tumor↗
PubMed2000

Pike. A nuclear gtpase that enhances PI3kinase activity and is regulated by protein 4.1N.

While cytoplasmic PI3Kinase (PI3K) is well characterized, regulation of nuclear PI3K has been obscure. A novel protein, PIKE (PI3Kinase Enhancer), interacts with nuclear PI3K to stimulate its lipid kinase activity. PIKE encodes a 753 amino acid nuclear GTPase. Dominant-negative PIKE prevents the NGF enhancement of PI3K and upregulation of cyclin D1. NGF treatment also leads to PIKE interactions with 4.1N, which has translocated to the nucleus, fitting with the initial identification of PIKE based on its binding 4.1N in a yeast two-hybrid screen. Overexpression of 4.1N abolishes PIKE effects on PI3K. Activation of nuclear PI3K by PIKE is inhibited by the NGF-stimulated 4.1N translocation to the nucleus. Thus, PIKE physiologically modulates the activation by NGF of nuclear PI3K.

Adenosine Triphosphate↗
PubMed2000

Cytogenetic study of workers exposed to chromium compounds.

The frequency of sister chromatid exchanges (SCEs), high SCE frequency cells (HFCs), and genetic polymorphism of genotypes glutathione S-transferase (GST) M1 and T1 were analyzed in peripheral lymphocytes of 35 workers occupationally exposed to chromium (Cr) and 35 matched control group. Results showed that workers exposed to Cr showed 6.07 SCE/cell, as compared to 4.76 SCE/cell for the control group (p<0.01). Smokers showed a statistically significant higher frequency of SCE than non-smokers in both groups. The work duration of Cr workers was an important factor. Workers exposed for more than 5 years showed a significantly higher level of SCEs (p<0.05). Workers exposed to Cr for 5 or more years had higher HFC rates (51.4%) than those exposed for less than 5 years (22.9%), with an odds ratio of 4.5 times than those exposed for less than 5 years. In HFC analysis, Cr workers who smoked showed a higher level of HFC (60%) than the control group (5.7%) and also had a higher odds ratio (60.4) compared with the control group. Among non-smokers, the odds ratio was 9.0. Another objective of this study is to investigate the relationship between SCE and genetic polymorphisms of GST M1 and T1 in Cr workers. The results showed that the incidence of GSTM1 null genotype was 60% in the control group and 77.1% in Cr workers, and percentages of GSTT1 deletion were 42.9% and 62.9% in control and exposed individuals, respectively. There was a slightly increased frequency of SCE among Cr workers with GSTM1 null genotype as opposed to non-null genotype individuals. A similar result was seen among the control group; however, there were no statistically significant differences. In conclusion, the current study found the positive induction of SCE in workers who smoked or/and were exposed to Cr. However, different GST genotypes did not influence the level of cytogenetic damage between groups. Despite slight variation in numbers, they all appear to be not different.

Adult↗
PubMed2000

Adeno-associated virus major Rep78 protein disrupts binding of TATA-binding protein to the p97 promoter of human papillomavirus type 16.

Adeno-associated virus type 2 (AAV) is known to inhibit the promoter activities of several oncogenes and viral genes, including the human papillomavirus type 16 (HPV-16) E6 and E7 transforming genes. However, the target elements of AAV on the long control region (LCR) upstream of E6 and E7 oncogenes are elusive. A chloramphenicol acetyltransferase assay was performed to study the effect of AAV on the transcription activity of the HPV-16 LCR in SiHa (HPV-positive) and C-33A (HPV-negative) cells. The results reveal that (i) AAV inhibited HPV-16 LCR activity in a dose-dependent manner, (ii) AAV-mediated inhibition did not require the HPV gene products, and (iii) the AAV replication gene product Rep78 was involved in the inhibition. Deletion mutation analyses of the HPV-16 LCR showed that regulatory elements outside the core promoter region of the LCR may not be direct targets of AAV-mediated inhibition. Further study with the electrophoretic mobility shift assay demonstrated that Rep78 interfered with the binding of TATA-binding protein (TBP) to the TATA box of the p97 core promoter more significantly than it disrupted the preformed TBP-TATA complex. These data thus suggest that Rep78 may inhibit transcription initiation of the HPV-16 LCR by disrupting the interaction between TBP and the TATA box of the p97 core promoter.

Cell Line↗
PubMed2000

Binary/ternary combined effects of vitamin K3 with other antitumor agents in nasopharyngeal carcinoma CG1 cells.

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Taiwan. To improve the treatment of NPC, we have extensively searched for effective combination chemotherapies. Our previous studies indicated that vitamin K3 (VK3) inhibits the growth of NPC CG1 cells in vitro. In this study, we further studied the binary/ternary combined effects of VK3 with other anticancer drugs against NPC cells. The antitumor effects of different VK3 combinations against CG1 cells were determined by using MTT assay, and the combined effects were evaluated by a taibologram, a modified isobolographic method being developed in our laboratory for the analyses of binary/ternary combinations of anticancer agents. Binary combinations of VK3 with doxorubicin (DOX), vinblastine (VBL), or 5-fluorouracil (5-FU) result in synergistic effects. For three-drug combinations, a remarkable synergy was found in the combination of VK3, VBL, and 5-FU. These in vitro results will provide useful information not only for further mechanistic studies and but also for future clinical trials of VK3-based cancer chemotherapy of NPC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26.

Approximately one quarter of the identified human serpin genes are cancer-related and clustered mainly at two distinct loci: 6p25 and 18q21. We have studied a novel serpin gene cluster at 3q26 containing at least two recently identified members: the pancreas-specific protease inhibitor, pancpin (PI14), and the brain-associated protease inhibitor, neuroserpin (PI12). In this, unlike a previous study, both PI14 and PI12 at 3q26 were found to consist of 9 exons and 8 introns and to share a perfectly conserved gene organization whose pattern is very different from that of the ov-serpin family. This distinct pattern appears identical in the genomic structures of human plasminogen activator inhibitor-1 (PAI1) at 7q21 and protease nexin 1 (PI7) at 2q33-35, confirming that these four genes in three different chromosomes form a discrete subset within the serpin superfamily. As in the other three members whose gene expression is altered during tumorigenesis, PI12 expression was found to be down-regulated in tumor brain tissues and in two brain cancer cell lines: U-87 MG and H4. By screening genomic libraries, we isolated two overlapping clones showing that the marker SGC32223 (centromere) is located within intron F of PI12 and the marker WI-10077 (telomere) is located downstream of the 3'-flanking region of PI14. This finding indicates that the distance between human PI14 and PI12 is approximately 100 kb, and hence we speculate that other tissue-specific cancer-related serpin genes are likely to reside within this 3q26.1 cluster region.

Amino Acid Sequence↗
PubMed1999

Vitamin K3 induces cell cycle arrest and cell death by inhibiting Cdc25 phosphatase.

Our early reports have indicated that vitamin K3 (VK3) exerts antitumour activity by inhibiting Cdk1 activity and overexpressing the c-myc gene to induce an apoptotic cell death. In the present study, we investigated the effect of VK3 on Cdc25 phosphatase, a Cdk1 activator and c-Myc-downstream protein. Increased protein level but decreased activity of Cdc25A phosphatase was found in cervical carcinoma SiHa cells treated with VK3 for 1 h and allowed to recover for 8, 24, 30 or 45 h. The binding of VK3 to Cdc25 phosphatase was proven by incubating [methyl-3H]-VK3 with the 27 kDa-catalytic domain of Cdc25A phosphatase at 35 degrees C for 2 h. We found that VK3 inhibited cyclin E expression at late G1 phase and cyclin A at G1/S transition of the aphidicolin-synchronised SiHa cells, but had no effect on Cdk2 and Cdk4. The inhibition of cyclins E and A expression was associated with cell cycle progression delay in the S phase. These results indicate that binding of VK3 to the catalytic domain of Cdc25 phosphatase results in the formation of inactive, hyperphosphorylated Cdk1 that subsequently induces cell cycle arrest, leading to cell death. These findings suggest a possible therapeutic strategy, with VK3 serving as a potential antagonist to tumours expressing high levels of proteins containing cysteine such as oncogenic Cdc25A phosphatase.

Apoptosis↗
PubMed1999

Suppression of tumorigenicity in cervical carcinoma HeLa cells by an episomal form of adeno-associated virus.

To compare the oncosuppressive activity of integrated and episomal adeno-associated virus (AAV), two Epstein-Barr virus (EBV) derived episomal form vectors, p205 and p220, were used to generate plasmids containing episomal AAV. HeLa cells transfected with p205, p220, and the plasmids with forward (pA205-1, pA220-1) and reverse (pA205-1, pA220-2) orientation of inserted AAV DNA were designated H205, H220, HA205-1, HA220-1, HA205-1, and Ha220-2, respectively. The respective average copy numbers of pA205 and pA220 per cell are 4.9-6.9 and 4.3. The AAV-transfected HeLa cells displayed growth inhibition when compared to parental and the vector-transfected HeLa cells. Nude mice assay showed that the tumor size from HA205-1 and HA205-2 cells were 11.3 and 22.6%, and those from HA220-1 and HA220-2 cells were 54.8 and 57.3%, respectively, when compared to parental HeLa cells. HA205-1 cells containing forward AAV insert exerted more oncosuppressive effect than HA205-2 cells containing reverse AAV insert. Our data indicate that the episomal AAV can exert oncosuppressive activity as compared to the integrated AAV in HeLa cells.

Animals↗
PubMed1999

Alien hand syndrome: report of two cases.

Alien hand syndrome (AHS) refers to the occurrence of apparently purposeful movements in the hand which are independent of volitional control. Two subtypes of AHS have been proposed: frontal AHS, with grasp reflex and compulsive manipulation of tools by the dominant hand, and callosal AHS, which occurs in the nondominant hand and is characterized mainly by intermanual conflict. Here, we report two cases of frontal-type alien hand syndrome with symptoms of reflexive grasping, impulsive groping, and apraxia (in case 1), and compulsive manipulation of tools (in case 2). Brain computed tomography revealed a left anterior cerebral artery (ACA) territory infarct and multiple small infarcts of both hemispheres in patient 1 and a left ACA infarct in patient 2. The involuntary movements were bothersome to these patients in their daily activities. Both patients attended conventional physical and occupational therapies, and patient 2 received additional biofeedback training. Follow-up studies showed the spontaneous grasping behavior was still present in patient 1 and AHS had subsided in patient 2. We also describe a potentially effective technique involving biofeedback for patients with alien hand syndrome.

Aged↗
PubMed1998

Menadione (vitamin K3) enhances the mitogenic signal of epidermal growth factor via extracellular signal-regulated kinases.

The effects of vitamin K3 (VK3) on DNA synthesis, cell proliferation and mitogen-activated protein kinase pathway were investigated in G0-arrested NIH 3T3 fibroblasts. VK3 (5 microM) alone stimulates DNA synthesis by 40% and moderately increases the mitogenic effects of EGF, which is preceded by a rapid phosphorylation of the extracellular signal-regulated kinases (ERKs). At 20 microM, VK3 had an antiproliferative effect. VK3 alone (5 and 50 microM) or in concert with EGF increases the activity of ERK2 (by 2.5 and 5 fold, respectively). Our studies demonstrate that the activation of ERKs by VK3 alone, or VK3 plus EGF can promote either stimulatory or inhibitory effects on the mitogenic signal.

3T3 Cells↗